吉田 憲司

OBJECTIVE: Hepatic fibrosis has recently been evaluated using ultrasonography or magnetic resonance elastography. Although the shear wave velocity (SWV) obtained using point shear wave elastography (pSWE) provides a valuable measure of fibrosis, underlying steatosis may affect its measurement. METHODS: Using hepatic fibrosis samples, this study evaluated the effect of steatosis on the shear wave velocity of pSWE (Vs) and viscoelastic properties (assessed by dynamic mechanical analysis) of rat liver. Fifty rats with various grades of steatosis and fibrosis underwent open abdominal in vivo Vs measurements using a commercial ultrasound scanner. The mechanical properties of hepatic tissue were also characterized under ex vivo conditions using dynamic mechanical analysis and the Zener model of viscoelasticity. RESULTS: Fibrosis and steatosis progression influenced Vs and elasticity. The SWV computed using the Zener model and Vs showed a substantial correlation (r > 0.8). Fibrosis progression increased SWV. Steatosis was also related to SWV. Steatosis progression obscured the SWV change associated with fibrosis progression. CONCLUSION: We conclude that steatosis progression affects the evaluation of fibrosis progression. This finding could aid discrimination of non-alcoholic steatohepatitis from non-alcoholic fatty liver disease using SWV.

Detection of tumors and regional lymph nodes during surgery has been proposed in the diagnosis of lymphatic metastasis and the surgical treatment of malignant diseases. Giant cluster vesicles (GCVs), including liposomally formulated indocyanine green (LP-ICG) derivatives, are a possible candidate for agents to realize the two contradictory properties, i.e., retention in tissue for lesion-marking and trace for sentinel lymph nodes (SLNs) identification. We attempted to release the LP-ICG derivatives from GCVs using ultrasound contrast agents (UCAs) under ultrasound irradiation. An absorption spectrophotometer quantitatively evaluated the amounts of released LP-ICG derivatives. As a result, we demonstrated that it depended on conditions for sound pressure, burst length, and number density of UCAs, and had a sound pressure threshold independent of burst length and number density of UCAs. The results will aid to determine appropriate conditions to maximize the released amount of LP-ICG derivatives while keeping safety.

Introduction: Assessing the stage of liver fibrosis during the diagnosis and follow-up of patients with diffuse liver disease is crucial. The tissue structure in the fibrotic liver is reflected in the texture and contrast of an ultrasound image, with the pixel brightness indicating the intensity of the echo envelope. Therefore, the progression of liver fibrosis can be evaluated non-invasively by analyzing ultrasound images. Methods: A convolutional-neural-network (CNN) classification of ultrasound images was applied to estimate liver fibrosis. In this study, the colorization of the ultrasound images using echo-envelope statistics that correspond to the features of the images is proposed to improve the accuracy of CNN classification. In the proposed method, the ultrasound image is modulated by the 3rd- and 4th-order moments of pixel brightness. The two modulated images and the original image were then synthesized into a color image of RGB representation. Results and Discussion: The colorized ultrasound images were classified via transfer learning of VGG-16 to evaluate the effect of colorization. Of the 80 ultrasound images with liver fibrosis stages F1–F4, 38 images were accurately classified by the CNN using the original ultrasound images, whereas 47 images were classified by the proposed method.

Abstract Previous studies have shown that shear wave elastography of liver tissue can be unstable due to factors such as uncertainties in the acoustic radiation force (ARF) irradiation due to the influence of tissues near the surface and the complexity of the liver’s structure and its physical properties. This study aims to verify the influence of near-surface tissues on ARF and the effect of tissue structure on shear wave propagation and shear wave velocity (SWV) evaluation using the wave propagation simulations by the elastic finite-difference time domain method. It is found that the ARF becomes weakly focused on multiple locations due to refraction of longitudinal waves by near-surface tissues, and multiple shear waves of small amplitude are propagated. However, a macroscopic SWV assessment, as in clinical practice, reduces the influence of near-surface tissues because the microscopic assessment results are averaged over the near-surface tissues.

Abstract We attempted to visualize a single microbubble driven by acoustic radiation force using a combination of pulse inversion Doppler and plane wave imaging. Commercial microbubbles, Sonazoid^® underwent ultrasound exposure with a center frequency of 5.2 MHz, a pulse repetition frequency of 4 kHz, and a negative peak sound pressure of 1.59 MPa. It succeeded in separately detecting individual microbubbles with high sensitivity. The disappearance of freely-translating microbubbles could be observed as a broadened spectrum of Doppler signal, i.e. a pseudo-Doppler effect. However, the trend was not apparent in the case of wall-colliding microbubbles.

Abstract We compared the evaluation accuracy of amplitude envelope statistics under the transmission and reception conditions of compounded plane wave imaging (CPWI) and focused beam imaging (FBI). In a basic study using a homogeneous phantom, we found that the amplitude gradient in the depth direction and the point spread function in the lateral direction spread in the FBI reduced the accuracy of evaluation in amplitude envelope statistics. On the other hand, CPWI showed a more stable evaluation than FBI because of the elimination of sound field characteristics. In CPWI, the multi-Rayleigh model discriminated signals from two types of scatterer with high accuracy in the evaluation using phantoms mimicking fatty liver. It was confirmed that the combination of CPWI and the multi-Rayleigh model is effective for detecting early fatty liver disease. The results show that CPWI is effective for improving the robustness of amplitude envelope statistics.

High-frame-rate imaging with a clutter filter can clearly visualize blood flow signals and provide more efficient discrimination with tissue signals. In vitro studies using clutter-less phantom and high-frequency ultrasound suggested a possibility of evaluating the red blood cell (RBC) aggregation by analyzing the frequency dependence of the backscatter coefficient (BSC). However, in in vivo applications, clutter filtering is required to visualize echoes from the RBC. This study initially evaluated the effect of the clutter filter for ultrasonic BSC analysis for in vitro and preliminary in vivo data to characterize hemorheology. Coherently compounded plane wave imaging at a frame rate of 2 kHz was carried out in high-frame-rate imaging. Two samples of RBCs suspended by saline and autologous plasma for in vitro data were circulated in two types of flow phantoms without or with clutter signals. The singular value decomposition was applied to suppress the clutter signal in the flow phantom. The BSC was calculated using the reference phantom method, and it was parametrized by spectral slope and mid-band fit (MBF) between 4-12 MHz. The velocity distribution was estimated by the block matching method, and the shear rate was estimated by the least squares approximation of the slope near the wall. Consequently, the spectral slope of the saline sample was always around four (Rayleigh scattering), independently of the shear rate, because the RBCs did not aggregate in the solution. Conversely, the spectral slope of the plasma sample was lower than four at low shear rates but approached four by increasing the shear rate, because the aggregations were presumably dissolved by the high shear rate. Moreover, the MBF of the plasma sample decreased from -36 to -49 dB in both flow phantoms with increasing shear rates, from approximately 10 to 100 s-1. The variation in the spectral slope and MBF in the saline sample was comparable to the results of in vivo cases in healthy human jugular veins when the tissue and blood flow signals could be separated.

PURPOSE: The aim of this study was to elucidate the frequency dependence of the speed of sound (SoS) and attenuation coefficients in phantoms with controlled attenuation properties (scatterer density, scatterer size, absorption control material) and rat livers. METHODS: The frequency dependence of SoS and attenuation coefficients were evaluated with ultrasound (1-15 MHz) by observing multiple phantoms with different scatterer sizes, densities, and presence or absence of evaporated milk as absorbing media. Normal and fatty model rat livers were examined with the same protocol. RESULTS: The phantom results revealed that the scatterer density and SoS of the base media were the dominant factors causing the changes in SoS. Frequency dependence was not observed in SoS. Assessment of the attenuation coefficient showed that the frequency dependence was mainly affected by absorption attenuation when the scatterer was as small as a hepatocyte (i.e. ≤ 10 µm). Scattering attenuation was also observed to affect frequency dependence when the scatterer was as large as lipid droplets (i.e. ≤ 40 µm). CONCLUSION: Assuming a consistent size of the main scatterers in the evaluation medium, the frequency dependence of the SoS and attenuation coefficients may provide insight into the scatterer density and the contribution of absorption and scattering attenuation. Further studies in the higher frequency band (up to about 50 MHz) are expected to advance the clinical application of high-frequency ultrasound.

Abstract In a previous study, an annular-array transducer was employed to characterize homogeneous scattering phantoms and excised rat livers using backscatter envelope statistics and frequency domain analysis. A sound field correction method was also applied to take into account the average attenuation of the entire scattering medium. Here, we further generalized the evaluation of backscatter coefficient (BSC) using the annular array in order to study skin tissues with a complicated structure. In layered phantoms composed of two types of media with different scattering characteristics, the BSC was evaluated by the usual attenuation correction method, which revealed an expected large difference from the predicted BSC. In order to improve the BSC estimate, a correction method that applied the attenuation of each layer as a reference combined with a method that corrects based on the attenuation of the analysis position were applied. It was found that the method using the average attenuation of each layer is the most effective. This correction method is well adapted to the extended depth of field provided by an annular array.

Abstract This study investigates how the translational velocity of phospholipid-coated bubbles caused by acoustic radiation force depends on their size. The translations of bubbles with mean radii of 0.9–5 μm were experimentally evaluated at five ultrasound frequency conditions (3.5, 5, 7.5, 10, and 15 MHz). We compared experimental data with theoretical prediction using a viscoelastic interfacial rheological model and a model suitable for high amplitude oscillation. The results suggested that the translation of bubbles could be enhanced for a mean radius of 1–3 μm but echo intensity could not.

Abstract In contrast enhancement ultrasound (CEUS), the vasculature image can be formed from nonlinear echoes arising from microbubbles in a blood flow. The use of binary-coded pulse compression is promising for improving the contrast of CEUS images by suppressing background noise. However, the amplitudes of nonlinear echoes can be reduced, and sidelobes by nonlinear echoes can occur depending on the binary code. Optimal Golay codes with slight nonlinear-echo reduction and nonlinear sidelobe have been proposed. In this study, CEUS images obtained by optimal Golay pulse compression are evaluated through experiments using Sonazoid microbubbles flowing in a tissue-mimicking phantom.

This study investigated the ability of in vivo quantitative ultrasound (QUS) assessment to evaluate lymphedema severity compared with the gold standard method, the International Society of Lymphology (ISL) stage. Ultrasonic measurements were made around the middle thigh (n = 150). Radiofrequency data were acquired using a clinical scanner and 8-MHz linear probe. Envelope statistical analysis was performed using constant false alarm rate processing and homodyned K (HK) distribution. The attenuation coefficient was calculated using the spectral log-difference technique. The backscatter coefficient (BSC) was obtained by the reference phantom method with attenuation compensation according to the attenuation coefficients in the dermis and hypodermis, and then effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated with a Gaussian model. Receiver operating characteristic curves of QUS parameters were obtained using a linear regression model. A single QUS parameter with high area under the curve (AUC) differed between the dermis (ESD and EAC) and hypodermis (HK) parameters. The combinations with ESD and EAC in the dermis, HK parameters in the hypodermis and typical features (dermal thickness and echogenic regions in the hypodermis) improved classification performance between ISL stages 0 and ≥I (AUC = 0.90 with sensitivity of 75% and specificity of 91%) in comparison with ESD and EAC in the dermis (AUC = 0.82) and HK parameters in the hypodermis (AUC = 0.82). In vivo QUS assessment by BSC and envelope statistical analyses can be valuable for non-invasively classifying an extremely early stage of lymphedema, such as ISL stage I, and following its progression.

Abstract A blood mimicking fluid (BMF) is imperative for the evaluation of Doppler ultrasound. Doppler ultrasound still causes errors due to some artifacts such as aliasing and presence of grating lobes. One of the other velocimeters is the optical particle image velocimeter (PIV). This study initially developed an in vitro measurement system for analyzing flowing BMF with ultrasonic and optical PIVs. The acoustic properties such as speed of sound, attenuation, and backscatter coefficient of BMF equivalent to the human blood, used for both ultrasonic and optical PIVs were analyzed in a frequency range of 4-12 MHz. The velocity profiles were estimated by ultrasonic and optical PIVs using a block matching method. A difference between velocities obtained by ultrasonic and optical data was within 4.0% using BMF with 20 µm polyamide particle at 0.2% concentration that realized the acoustic properties and speckle patterns similar to those in ultrafast ultrasound blood flow imaging.

高速超音波イメージングは血管や循環器系における血流速ベクトル評価に応用されている.流速推定値は,エイリアシングやグレーティングローブなどの超音波固有のアーチファクトによって推定誤差が表れる場合がある.粒子分布を可視化し速度計測を行える他のシステムの一つとして,光学的粒子画像追跡法(particle image velocimetry:PIV)が挙げられる.本報告では超音波・光学システムを併用した流れ場観察システムを構築し,複数種の血液模擬溶液の流速を評価した.また,超音波・光学システムでの安定した速度推定が可能な粒子径や濃度条件を整理するとともに,基礎的な音響特性(音速・減衰係数・後方散乱係数)を評価し,IEC規格が示す血液模擬溶液の推奨値と比較した.超音波および光学システムにおいて推定した流速は,直径20μmのポリアミド粒子が溶液中に0.2%存在している場合,同等(誤差4.0%)であるとともにIEC規格が示す音響特性の推奨値の範囲内かつ超音波像においてスペックルパタンが保持されていることを確認した.(著者抄録)

In previous studies, the double-Nakagami (DN) model has been proposed for fatty liver assessment and applied to in vivo rat livers and clinical data sets. The healthy liver structure filter (HLSF) method, which extracts non-healthy areas using two DN parameters, has also been proposed. In this paper, we first verify the accuracy of the DN model and the HLSF method for acoustic fields at 15 and 5 MHz, which were reproduced using numerical simulation. We then apply the method to clinical data sets of livers observed using a frequency of 3 MHz and investigate the method's clinical usefulness. A positive correlation (r = 0.28) was found between the ratio of the non-healthy area and fat mass. Although the results were inferior to the results produced using 15 MHz ultrasound (r = 0.96), we found that it was possible to detect the difference between a normal liver and a fatty liver even at a lower frequency. (C) 2021 The Japan Society of Applied Physics

We investigated the differences between the transmission (Tx)/reception (Rx) sound fields for target and reference signals using a reference phantom method (RPM) to assess the stability of backscattering coefficient (BSC) evaluation. A clinical ultrasound scanner and two types of phased linear array transducer with low and high frequencies were used to evaluate the BSCs for two types of homogenous phantom with different attenuation coefficients and BSCs. Different Tx/Rx sound fields were reproduced using different combinations of Tx focus depths and aperture sizes. Target signals with Tx conditions that were both the same as and different from those for the reference signals were used to produce signals with different Tx/Rx sound fields. The differences in the Tx/Rx sound fields affected the depth dependence of the evaluated BSC. It was concluded that this can be a factor creating variation in the BSC for homogenous targets.

Previous studies have shown that evaluation results of shear wave elastography were unstable due to factors such as liver structure and complexity of physical properties. The present study attempts to verify the influence of liver microstructure (fat droplets and fibrous tissue) on the shear wave and shear wave velocity (SWV) evaluation using a shear wave propagation simulation by the elastic finite-difference time-domain method. It was found that disruption of the shear wave causes variations in the SWV of the liver around fat droplets, and the SWV of the fibrous tissue depends on the shear wave propagation direction and the tissue shape. In a nonalcoholic steatohepatitis liver, which contains fat and fiber, the influences of these two tissues are synergistically reflected in the SWV evaluation.

Lipid-coated microbubbles (MBs) with an indocyanine green (ICG) derivative were fabricated for ultrasound and near-infrared (NIR) fluorescence dual imaging. We characterized the NIR-fluorescence intensity, stability and viscoelastic properties of the encapsulating lipid shell, focusing on the influence of the ICG derivative and lipid compositions. In terms of the NIR fluorescence intensity, the fluorescence intensity of the MBs (with the ICG derivative) was significantly affected by the lipid composition of the MB shell. Regarding the contrast agent used for ultrasound imaging, the stability of the MBs and viscoelastic properties of shell also depended on the lipid compositions, while the incorporation of the ICG derivative into the MB shells had a negligible effect. The performance of this contrast agent for ultrasound and NIR fluorescence dual-imaging exhibited a significant trade-off relationship for the lipid composition.

A better understanding of ultrasound scattering in a three-dimensional (3D) medium can provide more accurate methods for ultrasound tissue characterization. The possibility of using two-dimensional impedance maps (2DZMs) based on correlation coefficients has shown promise in the case of isotropic and sparse medium [Luchies and Oelze, J. Acoust. Soc. Am. 139, 1557-1564 (2016)]. The present study investigates the use of 2DZMs in order to quantify 3D scatterer properties of dense media from two-dimensional (2D) histological slices. Two 2DZM approaches were studied: one based on the correlation coefficient and the other based on the 2D Fourier transform of 2DZMs. Both 2DZM approaches consist in estimating the backscatter coefficient (BSC) from several 2DZMs, and then the resulting BSC was fit to the theoretical polydisperse structure factor model to yield 3D scatterer properties. Simulation studies were performed to evaluate the ability of both 2DZM approaches to quantify scattering of a 3D medium containing randomly distributed polydisperse spheres or monodisperse ellipsoids. Experimental studies were also performed using the histology photomicrographs obtained from HT29 cell pellet phantoms. Results demonstrate that the 2DZM Fourier transform-based approach was more suitable than the correlation coefficient-based approach for estimating scatterer properties when using a small number of 2DZMs.

Clinical ultrasound is widely used for quantitative diagnosis. To clarify the relationship between anatomical and acoustic properties, high resolution imaging using high-frequency ultrasound (HFU) is required. However, when tissue properties are evaluated using HFU, the depth of field (DOF) is limited. To overcome this problem, an annular array transducer, which has a simple structure and produces high-quality images, is applied to HFU measurement. In previous phantom experiments, we demonstrated that the HFU annular array extends the DOF compared to that of a single-element transducer for quantitative ultrasound (QUS) analysis. Here, we extend that work by applying QUS methods to an ex vivo rat liver. The present study demonstrates that an annular array extends the region and improves the resolution for tissue characterization for an excised healthy rat liver. Amplitude envelope statistics and spectral-based analysis are used as QUS methods. (C) 2020 The Japan Society of Applied Physics

We studied the effect of acoustic and histopathological features on the ultrasound backscatter properties of lymphedema (LE) dermis. Experimental effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were calculated from a backscatter coefficient using the reflector method for backscattered signals. Predicted parameters were also analyzed using two-dimensional Fourier transforms of the acoustic impedance and histopathological distributions. Backscattered signals were obtained from ex vivo human tissues negative (n = 5) and positive (n = 5) for LE using a laboratory-made scanner with a 14 MHz transducer. Acoustic impedance was analyzed using scanning acoustic microscopy with a 68 MHz transducer, and histopathological features, such as fiber number density and thickness, were assessed with digital histopathology. Both experimental and predicted EACs showed differences (in the range 25.7%-102%) between negative and positive LE. Although the mean and standard deviation of the acoustic impedance were related to the difference in EACs, the ESD and histopathological features were the same regardless of the presence of LE. (C) 2020 The Japan Society of Applied Physics

Contrast-enhanced ultrasound imaging using acoustic radiation force, called contrast-enhanced active Doppler ultrasound (CEADUS) imaging, has been proposed for visualizing lymph channels filled with stationary fluid. Based on optical observations and acoustical evaluation, the behaviour of bubbles in a simulated channel during ultrasound exposure was investigated under four conditions for negative peak sound pressure (P-np), at centre frequency of ultrasound and pulse repetition frequency of 15 MHz and 1 kHz, respectively. There was good correlation between the time changes of mean translational velocity for optical evaluation (V-OPT) and acoustical evaluation (V-US). In addition, the maxima of V-OPT and V-US were correlated (R = 0.665) and showed a similar trend proportional to the square of Pnp. These results strongly suggest that the acoustically-evaluated bubble translation has information equal to optically-evaluated one, meaning that the simultaneous observation system is useful to understand the bubble behaviours under CEADUS imaging. (C) 2020 The Japan Society of Applied Physics

Quantitative ultrasound (QUS) methods have been widely used for soft tissue characterization. Spatial resolution (i.e. ultrasound frequency) is an important factor for QUS methods. In a previous study, a double Nakagami (DN) distribution model to echo signals from fatty livers using a 15 MHz transducer was used to permit fine-resolution QUS. This study used a filtering approach to quantify steatosis progression using three QUS parameters obtained by fitting a DN distribution model to experimental envelope data. The filter was designed using QUS parameters obtained from three healthy liver. A strong correlation (r = 0.96, p < 0.001) was found between histologically quantified steatosis percentage and the percentage of the liver having non-healthy liver features. This approach was able to successfully diagnose fatty livers (>20% steatosis percentage) in a dataset of 12 livers ranging from 0% to 90% steatosis. (C) 2020 The Japan Society of Applied Physics

Purpose Radio-frequency (RF) signals from the most dominant scatterer in a dermis, i.e., collagen fibers, are collected as backscattered signals. We aim to confirm the frequency dependence of the spatial distribution of features in ultrasound images, as well as the attenuation coefficient (AC) and backscatter coefficient (BSC) of skin tissue without [LE (-)] and with lymphedema [LE (+)]. Methods Measurement samples (n = 13) were excised from human skin tissue with LE (-) and middle severity LE (+). A laboratory-made scanner and single-element concave transducers (range 9-47 MHz) were used to measure RF data. A localized AC was computed from the normalized power spectrum using the linear least squares technique. The reflector method and compensation technique of the attenuation of tissue were applied to calculate the BSC. In addition, effective scatterer diameter (ESD), effective acoustic concentration (EAC), and integrated BSC (IBS) were calculated from the BSC as the benchmark to differentiate LE (-) and LE (+) tissues. Results High-frequency ultrasound displayed different echogenicity and texture compared between LE (-) and LE (+) in all transducers. The AC for LE (-) (0.22 dB/mm/MHz) and LE (+) (0.29 dB/mm/MHz) was comparable. BSC in LE (-) and LE (+) increased linearly with each transducer. The difference of intercept of the BSC between LE (-) and LE (+) indicated that both EAC and IBS of LE (+) were higher than that of LE (-). In contrast, ESD correlated with the slope of the BSC demonstrated the same tendency for both LE (-) and LE (+). These tendencies appeared for each transducer independent of the frequency bandwidth. Conclusion Frequency independence of AC and BSC in LE (-) and LE (+) was confirmed. Several 9- to 19-MHz ultrasound beams are sufficient for BSC analysis to discriminate LE (-) and LE (+) in terms of the penetration depth of the ultrasound.

Purpose The backscatter coefficient (BSC) indicates the absolute scatterer property of a material, independently of clinicians and system settings. Our study verified that the BSC differed among the scanners, transducers, and beamforming methods used for quantitative ultrasound analyses of biological tissues. Methods Measurements were performed on four tissue-mimicking homogeneous phantoms containing spherical scatterers with mean diameters of 20 and 30 mu m prepared at concentrations of 0.5 and 2.0 wt%, respectively. The BSCs in the different systems were compared using ultrasound scanners with two single-element transducers and five linear high- or low-frequency probes. The beamforming methods were line-by-line formation using focused imaging (FI) and parallel beam formation using plane wave imaging (PWI). The BSC of each system was calculated by the reference phantom method. The mean deviation from the theoretical BSC computed by the Faran model was analyzed as the benchmark validation of the calculated BSC. Results The BSCs calculated in systems with different properties and beamforming methods well concurred with the theoretical BSC. The mean deviation was below +/- 2.8 dB on average, and within the approximate standard deviation (+/- 2.2 dB at most) in all cases. These variations agreed with a previous study in which the largest error among four different scanners with FI beamforming was 3.5 dB. Conclusion The BSC in PWI was equivalent to those in the other systems and to those of FI beamforming. This result indicates the possibility of ultra-high frame-rate BSC analysis using PWI.

In this report, a method is proposed to quantify the translation of ultrasound contrast agent (UCA) microbubbles driven by acoustic radiation for the detection of channels filled with stationary fluid. The authors subjected UCA microbubbles in a channel with diameters of 0.1 and 0.5 mm to ultrasound pulses with a center frequency of 14.4 MHz. The translational velocity of the UCA microbubbles increased with the sound pressure and pulse repetition frequency (PRF) of the transmitted ultrasound. The mean translational velocity reached 0.75 mm/s at a negative peak sound pressure of 2.76 MPa and a PRF of 2 kHz. This trend agreed with the theoretical prediction, which indicated that the translational velocity was proportional to the square of the sound pressure and the PRF. Furthermore, an experiment was carried out with a phantom that mimics tissue and found that the proposed method aided in detection of the channel, even in the case of a low contrast-echo to tissue-echo ratio. The authors expect to develop the proposed method into a technique for detecting lymph vessels.

Microbubbles shelled with soft materials are expected to find applications as ultrasound-sensitive drug delivery systems, including through sonoporation. Microbubbles with specific vibrational characteristics and long intravascular persistence are required for clinical uses. To achieve this aim, the kinetics of the microbubble shell components at the gas/liquid interface while being subjected to ultrasound need to be better understood. This paper investigates the vibration characteristics and lifetime of single microbubbles coated with a poloxamer surfactant, Pluronic F-68, and 1,2-dimyristoyl-snglycero-3-phosphocholine (DMPC) under ultrasound irradiation. Air-and perfluorohexane (PFH)-filled microbubbles coated with Pluronic F-68 and DMPC at several concentrations (0 to 10(-2) mol L-1) were produced. An optical measurement system using a laser Doppler vibrometer and microscope was used to observe the radial vibration mode of single microbubbles. The vibrational displacement amplitude and resonance radius of Pluronic- or DMPC-coated microbubbles were found to depend very little on the concentrations. The resonance radius was around 65 mu m at 38.8 kHz under all the experimental conditions investigated. The lifetime of the microbubbles was investigated simultaneously by measuring their temporal change in volume, and it was increased with Pluronic concentration. Remarkably, the oscillation amplitude of the bubble has an effect on the bubble lifetime. In other words, larger oscillation under the resonance condition accelerates the diffusion of the inner gas.

High-frequency ultrasound (HFU, >20 MHz) and quantitative ultrasound (QUS) methods permit a means to understand the relationship between anatomical and acoustic characteristics. In our previous research, we showed that analyzing the acoustic scattering with HFU was an effective method for noninvasive diagnosis. However, the depth of field (DOF) of HFU transducers was limited, which constrains the range of QUS analysis. In this study, we seek to improve the accuracy of HFU, QUS-based parameters on the envelope statistics and frequency-based analysis by using an annular array that allows for an extended DOF. A 20-MHz annular-array transducer with five elements was employed to obtain signals which were beamformed in post-processing. Two kinds of low concentration scattering phantoms were scanned with 30-μm step size. Two QUS analysis techniques were employed: the Nakagami distribution and the reflector method. The results demonstrated that the annular array provides a stable analysis over an extended axial range.

We aim to develop an ultrasonic tissue characterization method for the follow-up of healing ulcers by diagnosing collagen fibers properties. In this paper, we demonstrated a computer simulation with simulation phantoms reflecting irregularly distributed collagen fibers to evaluate the relationship between physical properties, such as number density and periodicity, and the estimated characteristics of the echo amplitude envelope using the homodyned-K distribution. Moreover, the consistency between echo signal characteristics and the structures of ex vivo human tissues was verified from the measured data of normal skin and nonhealed ulcers. In the simulation study, speckle or coherent signal characteristics are identified as periodically or uniformly distributed collagen fibers with high number density and high periodicity. This result shows the effectiveness of the analysis using the homodyned-K distribution for tissues with complicated structures. Normal skin analysis results are characterized as including speckle or low-coherence signal components, and a nonhealed ulcer is different from normal skin with respect to the physical properties of collagen fibers. (C) 2018 The Japan Society of Applied Physics

Many methods for the analysis of amplitude envelope statistics have been proposed in recent decades to enable echo signal characterization and realize quantitative diagnosis based on these statistics. In the statistical analysis of ultrasound signals, the spatial resolution of the signal is an important factor. An analysis method that offers higher sensitivity than the current analysis model is required to allow the effective use of recently developed high-resolution ultrasonic diagnostic equipment. In this study, we propose a multi-amplitude envelope statistical model called the double Nakagami probability density function (PDF) model that assumes the physical structure of fatty liver disease under high-frequency ultrasound excitation. Application of the proposed model to actual rat livers demonstrated that it was possible to evaluate fatty liver disease at an early stage with a lower scatterer density than that of a normal liver. However, it is difficult to detect the disease at this stage using existing technology. (C) 2018 The Japan Society of Applied Physics

Choosing an appropriate dynamic range (DR) for acquiring radio frequency (RF) data from a high-frequency-ultrasound (HFU) system is challenging because signals can vary greatly in amplitude as a result of focusing and attenuation effects. In addition, quantitative ultrasound (QUS) results are altered by saturated data. In this paper, the effects of saturation on QUS estimates of effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were quantified using simulated and experimental RF data. Experimental data were acquired from 69 dissected human lymph nodes using a single-element transducer with a 26-MHz center frequency. Artificially saturated signals (x(c)) were produced by thresholding the original unsaturated RF echo signals. Saturation severity was expressed using a quantity called saturate-signal-to-noise ratio (SSNR). Results indicated that saturation has little effect on ESD estimates. However, EAC estimates decreased significantly with decreasing SSNR. An EAC correction algorithm exploiting a linear relationship between EAC values over a range of SSNR values and l(1)-norm of xc (i.e., the sum of absolute values of the true RF echo signal) is developed. The maximal errors in EAC estimates resulting from saturation were -8.05, -3.59, and -0.93 dB/mm(3) with the RF echo signals thresholded to keep 5, 6, and 7-bit from the original 8-bit DR, respectively. The EAC correction algorithm reduced maximal errors to -3.71, -0.89, and -0.26 dB/mm3 when signals were thresholded at 5, 6, and 7-bit, respectively.

Quantitative assessment of the material properties of ocular tissues can provide valuable information for investigating several ophthalmic diseases. Quantitative acoustic microscopy (QAM) offers a means of obtaining such information, but few QAM investigations have been conducted on human ocular tissue. We imaged the optic nerve (ON) and iridocorneal angle in 12-mu m deparaffinized sections of the human eye using a custom-built acoustic microscope with a 250-MHz transducer (7-mu m lateral resolution). The two-dimensional QAM maps of ultrasound attenuation (), speed of sound (c), acoustic impedance (Z), bulk modulus (K), and mass density () were generated. Scanned samples were then stained and imaged by light microscopy for comparison with QAM maps. The spatial resolution and contrast of scanning acoustic microscopy (SAM) maps were sufficient to resolve anatomic layers of the retina (Re); anatomic features in SAM maps corresponded to those seen by light microscopy. Significant variations of the acoustic parameters were found. For example, the sclera was 220 MPa stiffer than Re, choroid, and ON tissue. To the authors' knowledge, this is the first systematic study to assess c, Z, K, , and of human ocular tissue at the high ultrasound frequencies used in this study.

DNA double-strand breaks (DSBs) caused by ultrasound were evaluated in a quantitative manner by single-molecule fluorescence microscopy. We compared the effect of time-interval (or pulse) sonication to that of continuous wave (CW) sonication at a fixed frequency of 30 kHz. Pulses caused fewer DSBs than CW sonication under the same total input ultrasound energy when the pulse repetition period was above the order of a second. In contrast, pulses caused more DSBs than CW sonication for pulse widths shorter than a second. These effect of ultrasound on DNA were interpreted in terms of the time-dependent decay in the probability of breakage during the duration of a pulse. We propose a simple phenomenological model by considering a characteristic decay in the probability of DSBs during single-pulse sonication, which reproduces the essence of the experimental trend. In addition, a data analysis revealed a characteristic scaling behavior between the number of pulses and the number of DSBs.

Acoustic properties of free fatty acids present in the liver were studied as a possible basis for noninvasive ultrasonic diagnosis of non-alcoholic steatohepatitis. Acoustic impedance was measured for the following types of tissue samples: Four pathologic types of mouse liver, five kinds of FFAs in solvent and five kinds of FFAs in cultured Huh-7 cells. A transducer with an 80-MHz center frequency was incorporated into a scanning acoustic microscopy system. Acoustic impedance was calculated from the amplitude of the signal reflected from the specimen surface. The Kruskal-Wallis test revealed statistically significant differences (p < 0.01) in acoustic impedance not only among pathologic types, but also among the FFAs in solvent and in cultured Huh-7 cells. These results suggest that each of the FFAs, especially palmitate, oleate and palmitoleate acid, can be distinguished from each other, regardless of whether they were in solution or absorbed by cells. (C) 2016 World Federation for Ultrasound in Medicine & Biology.

Targeted microbubbles (TMBs) that specifically accumulate on target sites via biochemical bonds have been studied for using ultrasound diagnoses and therapies (e.g., ultrasound molecular imaging) in the research field. To understand the specific interactions between TMBs and their target molecules, a biosensor system with a quartz crystal microbalance (QCM) was constructed. In this system, TMBs become absorbed on their target molecule, which was fixed to the QCM surface via a self-assembled monolayer. Our previous studies showed that the system allowed the evaluation of the interaction between biotinylated MBs and the target molecule, streptavidin, by monitoring changes in the resonant frequency of QCM [Muramoto et al., Ultrasound Med. Biol., 40(5), 1027-1033 (2014)]. This paper investigates how the amount of streptavidin relates to the amount of absorbed biotinylated MBs. The amount of streptavidin on the QCM surface was evaluated by measuring the difference in its resonant frequency before and after the fixation of streptavidin. After which, the amount of absorbed MBs was also evaluated by measuring the frequency shift during the interaction between MBs and the target molecule. Our results showed a weak correlation between the amounts of bound MB and the density of streptavidin (correlation coefficient, r = 0.44), suggesting that the area density of target molecule can be evaluated by estimating the number density of TMBs. Published by AIP Publishing.

超音波による組織性状の定量診断技術が近年盛んに開発されているが，より高精度な診断のためには各種の生体組織が有する固有の音響特性と病理学的性質との詳細な関係性についての理解が必要不可欠である．本研究では，音波伝搬に関わるパラメータである音響インピーダンスと音速に着目し，病態の異なる4種類のラット肝臓（正常・脂肪肝・非アルコール性脂肪性肝炎（NASH）・硬変肝）について、中心周波数が80 MHzの振動子を搭載した超音波顕微鏡を用いて組織学的微細構造との関係を検討した．病理写真との比較により脂肪肝およびNASHでは脂肪滴が多数認められ，音響インピーダンスおよび音速はどちらも正常肝と比較してわずかではあるが統計的に低値，線維肝は高値となった（&lt;i&gt;p&lt;/i&gt;&lt;0.01）．この結果は，肝臓内に脂肪および線維が沈着することによる組織変性を反映していると考えられる．以上より，肝組織の変性状態を音響特性を指標として判定できる可能性が示唆された．